Understanding Chromosomes, Part II
By C.A. Sharp
(Reprint with permission, article first appeared in the Double Helix Network News).
Xs and Ys: Sex and the Single Chromosome
In our last article (Reporter, March, 2002 or Helex, Spring 1997), we looked at the conformation and faults of the chromosomes called autosomes. The others, sex chromosomes, are made of the same stuff, have the same parts and the same basic function as autosomes. They divide and separate during mitosis and meiosis, just like autosomes. But they also have important differences.
Like coat color or breed type, your dog’s gender is decided by its chromosomes and the genes they carry. Dogs, like all mammals, have a pair of sex chromosomes. Females have two like chromosomes, called "X," while males have a mixed pair, consisting of an X and a Y. This is why your stud dog is the one who must take the blame when you wanted to keep a dog pup and all you got were bitches. (Of course, if you own the stud and the bitch’s owners are the one who wanted a dog, you could steal Bill Cosby’s old line: It’s the fault of the one who last had it!)
The meaning of Xist-ence
X chromosomes are exactly like autosomal chromosomes in structure, with thousands of genes for a variety of traits spread along their length in the same DNA code used by autosomes. Most of these genes have nothing whatsoever to do with sexual characteristics.
Unlike the autosomal chromosomes, the X chromosome does not work in tandem with its pair partner. The Y chromosome contains very few genes, so in a male there is almost nothing for the genes on the X to pair with. Apparently, allowing both X chromosomes in females to remain active would cause problems because one of the X chromosomes is always turned off.
This happens during embryonic development and is accomplished by the action of a single gene, called Xist—for X inactive-specific transcript. On the active X chromosome, Xist is turned off; but on the inactive X, it is on. How each cell decides which X to activate is unknown. But, scientists do have some ideas on how Xist inactivates an entire chromosome.
Like other genes, Xist makes messenger RNA. Usually, messenger RNA leaves the nucleus of the cell to join up with the structures with which it makes proteins. But, like a herder sending out his dogs to bunch the flock, Xist produces RNA that remains in the nucleus and binds to sections of its own X chromosome deactivating it, probably by blocking the ability of other genes to make their own RNA. These RNA herding dogs always stick to their own "flock" and leave the active X chromosome alone.
Genes that do weird things—like making RNA that won’t leave the nucleus—are bound to draw the attention of scientists, so some interesting experiments have been done with Xist. The segment of DNA containing Xist lies near one end of the X chromosome. When researchers clipped this segment and spliced it to an autosomal chromosome, Xist turned on and deactivated the host chromosome. If Xist is spliced to the X chromosome of a male cell, it shuts that chromosome down, leaving the cell with no active X chromosome genes, other than itself.
There are no recorded cases of mammals with no active X chromosomes or only Y chromosomes.
Since the X chromosome contains genes for a wide variety of traits unrelated to sexual development, the embryo probably can’t develop without it. Apparently, you can live without any Y, but you can’t live without X. (We can only hope that this fact will elude political radicals on both sides of the women’s rights issue).
Y did that happen?
Y chromosomes are simple little souls. They contain very few genes, so few that researchers once thought there weren’t any. Genetically speaking, guys, you aren’t all there. But you do have a few dozen genes located on your Y chromosome, and all of them have to do with male sexual characteristics. Because of its comparative shortness and small number of genes, the Y chromosome was one of the first two human chromosomes to be mapped.
Without a Y, a male isn’t a male, with one exception we’ll talk about later. But if a male has too much Y, you might not want him as a neighbor or, in the case of a dog, in your kennel. Sometimes a glitch in the reproduction process causes a male to be born with one X and two or more Y chromosomes. These "Super Males" are often larger than the norm (over six feet) and are prone to aggressive and anti-social behavior. The more Ys, the worse the problem. "Super Males" are twenty times more likely to end up in prison than normal males.
The war between the Xs (and the Ys)
"Super Male" syndrome is not the only mismatch of X and Y chromosomes. Far from it. "Super Male" and the chromosomal defects that follow no doubt occur in dogs and other mammal species, but the bulk of the research has been done with humans, so the examples used here are mostly for people. The exact defects a dog might exhibit may vary, however most of these chromosome mismatches produce individuals that are sterile and have fertility problems, which is a concern for a dog breeder.
You might think "XXX" and "Super Females" have something to do with naughty movies. Nope. This also is a genetic condition. Females with three or more X chromosomes are described as hyper-feminine in behavior. They may have psychological and fertility problems. Like "Super Males," the more Xs a "Super Female" has, the more exaggerated her differences—broader hips, bigger breasts and (I hate to say it) lower IQs.
Occasionally, an individual may be XXY. "Kleinfelter’s Syndrome" individuals are male, often sterile and may suffer mental retardation, structural abnormalities and a tendency to truncal obesity (extra weight on the torso and long, thin arms and legs).
Those with just a single X, Turner’s Syndrome, are female. They generally stand less than five feet tall and are sterile. They may also have wide-set eyes and a wider than normal chest.
Sometimes an individual will be phenotypically male, but genotypically female. (This is that exception you were warned about). In these XXSR (XX sex reversal) individuals a small segment of the Y chromosome, called SRY, for sex-determining region Y, gets transposed onto an X chromosome. When this X is inherited by a daughter, she winds up looking like a son. Scientists have injected SRY into fertilized XX mouse eggs. The resulting mouse pups are phenotypically male.
XXSR, also called hermaphroditism, is known to occur in dogs, having been identified in at least a dozen breeds representing most of the AKC groups. Affected bitches may appear normal, but are likely to have both internal and external genital abnormalities. The vulva may be foreskin-shaped or positioned close to the belly. The clitoris may be enlarged, sometimes enough to protrude from the vulva. Internal abnormalities are very subtle and may not be obvious upon examination. At present the only sure way to diagnose an affected bitch is through microscopic examination of her ovaries. There is currently research being done at Cornell University to develop a DNA test that would diagnose affected individuals and indicate carriers. XXSR females are usually infertile, so the gene will have been passed by the sire in most cases.
If the male is an XXSR carrier, all of his daughters will be affected. If they are capable of breeding, they shouldn’t be allowed to. All of his sons will be clear and are safe to breed. The situation is less clear in the case of an XXSR bitch that has been able to whelp. At least half of her offspring will inherit her affected X chromosome.
An individual can also be phenotypically female and genotypically male. (And you thought this required surgery!) This condition is sex-linked. The recessive gene that causes it is located on the X chromosome.
Since males normally have only one X chromosome, they are much more prone to sex-linked defects than females. These defects are caused by genes located on the X chromosome.
If the gene is recessive, females are rarely affected because they usually have a dominant copy of the gene, too. Carrier females will give the disease to half of their sons, who will be affected because they have no dominant copy of the gene to counteract the recessive they have inherited. Half of the daughters of carrier females will also be carriers.
If an affected male has offspring, all his daughters will be carriers because they will get his X chromosome with the defective recessive gene. But all of his sons, who get his Y chromosome, will be normal.
Red-green color blindness in humans is a benign example of a six-linked recessive, but classic example it is anything but. Hemophilia A occurs in Australian Shepherds, but the textbook case about how this disease can devastate a bloodline features humans.
One could make a good argument that we owe our decades-long difficulties with the former Soviet Union to this gene. Queen Victoria was a prolific queen. She had nine children, enough to marry one off to almost every reigning house in Europe. As any dog breeder should know, there can be unfortunate fall-out from the over-use of popular individuals. The good Queen, as it turned out, was a carrier for hemophilia A. One of her sons had the disease. Since hemophilia had not been recorded in any of Victoria’s ancestors or relatives, it is assumed that the mutation developed with her.
One of her carrier daughters married a German duke and one of their daughters, also a carrier, married—you guessed it—the last Czar of Russia. Some historians have theorized that the imperial couple was so preoccupied with their hemophiliac son’s desperate illness, that matters of state were so neglected that the people began to think Lenin and Trotsky were offering a better deal.
Hemophilia B, or Christmas Disease, is also sex-linked. It has also been reported in Australian Shepherds, though both hemophilias are rare. If a breeder produces these, or any other sex-linked recessive diseases, affected males should not be bred. The dam should not be bred again, nor should her dam, maternal grand-dam, and so on. The full and half-sisters of the affected male out of the same dam should not be bred. Half of these sisters will not be carriers, but there is no way to test for the gene other than by breeding and hemophilia is a disease that shouldn’t happen to any dog.
Dominant six-linked disorders occur in both males and females. Similar to the case with recessive disorders, an affected male will pass it to all of his daughters and none of his sons, though in this case the daughters will be affected instead of carriers. Affected females can be either homozygous or heterozygous, depending on their dam’s status. They will pass the condition to all their offspring in the former case and half of them in the latter, regardless of gender.
There is only one, extremely rare, dominant sex-linked disorder identified in Aussies, affecting only one isolated family group. However, should such a disease occur in the general population, breeders should not breed any affected individual. By doing so, it will immediately be eliminated from the population.
A syndrome of cleft palate and multiple skeletal abnormalities was studied in a family of Aussies who were part of a research colony. All affected individuals descended from a single homozygous merle bitch. Females who carried the gene were only mildly affected, exhibiting polydactyly (extra toes and dewclaws) and, sometimes, extra teeth. For males the defect was lethal. Affected male offspring exhibited multiple skeletal problems, including abnormally short limbs, spondylosis (abnormally curved spine), spina bifida, grossly undershot jaw, double rows of teeth and cleft palate. Specific defects would vary from individual to individual, but all were sufficiently gross to result in the death of male puppies shortly after birth. Of several dozen affected male pups produced while this defect was under study, only one survived infancy. (Interesting, "Landshark," who got his name from his extra teeth, is still alive and healthy—though certainly not normal—more than a decade later. A credit, not doubt to the loving care he has received throughout his lifetime.)
Vive la difference!
Without X and Y chromosomes, and therefore sex, there could be no artificial selection (among other things we’ve come to know and love). Without artificial selection, there can be no dog breeding. But like everything else in this game of genetic craps we engage in, we can win or lose, depending on how those DNA dice tumble. The trick is to learn as much as you can about the rules of the game so you can minimize your losses.
Mastiffs — Gold
Coast Mastiffs — DeVine
Farms — Monarch
Last updated May 02, 2002